Case of the Week
Section Editors: Matylda Machnowska1 and Anvita Pauranik2
1University of Toronto, Toronto, Ontario, Canada
2BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
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January 7, 2021
Anti-Ma2 Antibody Paraneoplastic Encephalitis (Secondary to Mediastinal Seminoma)
- Background:
- Paraneoplastic encephalitis syndromes are inflammatory immune-mediated processes, associated with antibodies against antigens shared by tumor cells and native nonneoplastic neuronal cells (intraneuronal proteins), resulting from immunologic cross-reactivity. These autoantibodies vary with the underlying neoplasm.
- Anti-Ma2 antibodies are mostly related to testicular cancer, of which germinal cell tumors are most frequent.
- Extragonadal germinal cell tumors are extremely uncommon and often develop in the midline, with the anterior mediastinum being the most common site in adults.
- Clinical Presentation:
- Anti-Ma2 encephalitis may present as isolated or combined limbic, diencephalic, or brain stem encephalitis. Limbic encephalitis is characterized by psychiatric symptoms, seizures, short-term memory problems, and cognitive impairment. Diencephalic-hypothalamic dysfunction manifests as endocrine abnormalities, hyperthermia, hyperphagia, and somnolence. Brain stem encephalitis often causes ophthalmoplegia.
- The symptoms usually have an acute or subacute onset (days to weeks).
- Key Diagnostic Features:
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Hyperintense signal on FLAIR and T2-weighted images in limbic structures (amygdala, hippocampus, fornix, or cingulate gyrus) and diencephalic structures (thalamus, geniculate body, hypothalamus, reticular and subthalamic nucleus), usually with bilateral and relatively symmetric involvement
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Upper brain stem and basal ganglia abnormalities can also be found.
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Contrast enhancement is variable, indicating breakdown of the blood-brain barrier.
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In more than 60% of cases, the neurologic syndrome precedes the diagnosis of neoplasm; thus, a high degree of clinical suspicion is needed. Imaging findings are nonspecific but may suggest the diagnosis.
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Detection of specific autoantibodies (in serum or CSF) establishes the definitive diagnosis of paraneoplastic encephalitis; however, these are not always found. In these cases, alternative etiologies must be excluded for diagnosis.
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- Differential Diagnoses:
- Herpes simplex encephalitis: Mesial temporal lobe and insula are commonly involved, while basal ganglia are typically spared.
- Diffuse astrocytoma: Mass effect and asymmetric involvement
- Lymphoma: Restricted diffusion
- Other infectious or inflammatory diseases: HHV-6, EBV or flavivirus encephalitis, neurosyphilis and nonparaneoplastic autoimmune encephalitis (eg, anti-NMDA encephalitis)
- Treatment:
- Cancer treatment and immunotherapy (glucocorticoids, intravenous immune globulin, plasma exchange, cyclophosphamide or rituximab)
- Anti-Ma2 encephalitis usually has a better response to oncologic and immunologic treatment (one-third of patients will improve), in contrast with other paraneoplastic encephalitis syndromes.